Apr

20

Dr. Jules T. Mitchel, President of Target Health Inc. will be presenting on the topic of The Impact on the Industry of eSource Methodologies. Results from ongoing clinical programs will be presented as well as the results from recent regulatory inspections of sites using eSource methodologies to support a regulatory submission. The meeting will be held May 4-5, 2015 at the Wyndham Philadelphia Historic District, Philadelphia. Let us know if you will be attending so we can connect.

The following metric tells it all: of 45,723 eCRFs, there were 1,063 manual queries that resulted in 550 database changes, with 4 forms representing 69.7% of the changes:

Forms Entered

45,723

N (%)

Manual Queries (% of forms)

1,063 (2.3)

Date of Visit

316 (29.7)

Concomitant Medication

219 (20.6)

Other Medical History

116 (10.9)

Sitting Vital Signs

90 (8.47)

Changes to the database (% of Queries)

550 (1.2)

Trifoliate Orange Blossom and the Fibonacci sequence

Why is it that the number of petals in a flower is often one of the following numbers: 3, 5, 8, 13, 21, 34 or 55? For example, the lily has three petals, buttercups have five of them, the chicory has 21 of them, the daisy has often 34 or 55 petals, etc. Furthermore, when one observes the heads of sunflowers, one notices two series of curves, one winding in one sense and one in another; the number of spirals not being the same in each direction. Why is the number of spirals in general either 21 and 34, either 34 and 55, either 55 and 89, or 89 and 144? The same for pinecones. Finally, why is the number of diagonals of a pineapple also 8 in one direction and 13 in the other? Are these numbers the product of chance? No! They all belong to the Fibonacci sequence: 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, etc. (where each number is obtained from the sum of the two preceding numbers).

Note the 5 petals below photographed by our friend and colleague James Farley. Here is what he had to say: I went on a trail nearby work and spotted a beautiful flower growing from a plant with rather large green thorns. I almost totally missed it, as I was done walking the trail. What I figured out is that it is apparently not native! Took me some searching to figure out what it was! I worked hard at some compositions, trying to give enough context to give a sense of what I was experiencing there.

Apr

20

Onions are good prebiotics; they feed the probiotic organisms in our bodies

Bananas are another good prebiotic

Probiotics are living organisms, prebiotics are not.

A prebiotic is an ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health. Probiotics are microorganisms that are believed to provide health benefits when consumed. Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders and sachets containing the bacteria in freeze dried form are also available.

The term probiotic is currently used to name ingested microorganism associated with beneficial effects to humans and other animals. A recent study suggested that probiotics, by introducing good bacteria into the gut, may help maintain immune system activity, which in turn helps the body react more quickly to new infections. Antibiotics seem to reduce immune system activity as a result of killing off the normal gut 1) ___. In diet, prebiotics are typically compounds that pass through the upper part of the gastrointestinal tract and stimulate the growth and/or activity of advantageous bacteria that colonize the large 2) ___ by acting as a substrate for them. Researchers now focus on the distinction between short-chain, long-chain, and full-spectrum prebiotics. Short-chain prebiotics, e.g. oligofructose, contain 2-8 links per saccharide molecule and are typically fermented more quickly in the right side of the colon providing nourishment to the bacteria in that area. Longer-chain prebiotics, e.g. inulin, contain 9-64 links per saccharide molecule, and tend to be fermented more slowly, nourishing bacteria predominantly in the left-side colon. Full-spectrum prebiotics provide the full range of molecular link-lengths from 2-64 links per molecule, and nourish bacteria throughout the 3) ___, e.g. Oligofructose-Enriched Inulin (OEI). The majority of research done on prebiotics is based on full-spectrum prebiotics, typically using OEI as the research substance.

Some bacteria found in the gut produce vitamins. For example, they produce vitamin K, folic acid, and vitamin B12. Certain foods are known to be best for the good bacteria in your microbiome and help to keep a healthy balance in your 4) ___. Yogurt is a familiar source. In a probiotic study, done to see the effects of stress on intestinal flora, rats that were fed probiotics had little occurrence of harmful bacteria adhering to their intestines compared to rats that were fed sterile water. Other studies suggest that probiotics can help ease lactose intolerance. They also may help tame gas, diarrhea, and other digestive problems. You can pay extra for special digestive yogurt brands. On the label look for: live and active cultures. It is suggested that people use unpasteurized sauerkraut, because pasteurization (used to treat most supermarket sauerkraut) kills active, good bacteria. This sour, salty food — and the similar but spicy Korean dish, kimchi — is also loaded with immune-boosting vitamins that may help ward off infection. Miso is a popular breakfast food in 5) ___, this fermented soybean paste can get your digestive system moving. Probiotic-filled miso reportedly has more than 160 bacteria strains. It’s often used to make a salty soup that’s low in calories and high in B vitamins and protective antioxidants.

While cheese might be good for your digestion, not all probiotics can survive the journey through your stomach and intestines. Research finds that certain strains in some fermented soft cheeses, like Gouda, Port Salut, Muenster, Brie are hardy enough to make it. Cheese also may act as a carrier for probiotics, which may boost the 6) ___ system. According to legend, kefir, a fermented milk drink made with kefir “grains” (a yeast/bacterial fermentation starter), dates back to the shepherds of Eurasia’s Caucasus Mountains. These shepherds discovered that the milk they carried tended to ferment into a bubbly beverage. Thick, creamy, and tangy like yogurt, kefir has its own strains of probiotic bacteria, plus a few helpful yeast varieties.

San Francisco’s famous 7) ___ bread contains a probiotic that may help digestion. Be sure to try delicious sourdough bread, rolls, toast instead of plain white.

One of the easiest ways to get probiotics into your diet is by adding acidophilus milk, that’s been fermented with bacteria. Sometimes it’s labeled sweet acidophilus milk. Buttermilk, cultured with lactic acid bacteria is also rich in probiotics. Choose the right pickles for probiotics, naturally fermented kinds, where vinegar wasn’t used in the pickling process. A sea salt and water solution feeds the growth of good bacteria and may give sour pickles some digestive benefits. Tempeh is made from a base of fermented 8) ___. This Indonesian patty has a type of natural antibiotic that fights certain harmful bacteria. Tempeh is also high in protein. People often describe its flavor as smoky, nutty, and similar to a mushroom. You can marinate tempeh and use it in meals in place of meat.

Aside from being found in foods, probiotics come in supplements in capsule, tablet, powder, and liquid forms. Although they don’t provide the extra 9) ___that foods can offer, they’re convenient and offer a large number of the healthy bacteria. Some doctors are not well informed about probiotics, however medical schools are now including the subject of probiotics in their curriculums. While probiotic-foods have live bacteria, prebiotic foods feed the good bacteria already living in your gut. You can find prebiotics in items such as asparagus, Jerusalem artichokes, bananas, oatmeal, red wine, honey, maple syrup, and legumes. Try 10) ___ foods on their own or with probiotic foods to perhaps give the probiotics a boost.

Artichoke contains the bioactive agents apigenin, luteolin and inulin. C. scolymus also seems to have a bifidogenic effect on beneficial gut bacteria. Its effect in arresting pathogenic bacteria may be attributed to the notable presence of phenolic compounds. Both are higher in the baby anzio artichoke (Cyrnara scolymus). Artichoke leaf extract has proved helpful for patients with functional dyspepsia, and may ameliorate symptoms of irritable bowel syndrome. The inulin cannot be broken down by the human digestive system, but is metabolized by bacteria in the colon. Sources: sciencedaily.com; webmd.com; nih.gov; Wikipedia

Shakespeare was an English poet, playwright, actor, and widely regarded as the greatest writer in the English language and the world’s pre-eminent dramatist. He is often called England’s national poet and the Bard of Avon. His extant works, including some collaborations, consist of about 38 plays, 154 sonnets, two long narrative poems, and a few other verses, of which the authorship of some is uncertain. His plays have been translated into every major living language and are performed more often than those of any other playwright.

Shakespeare was born and brought up in Stratford-upon-Avon. While his birth date is not known, it is known that he was baptized on 26 April 1564. At the age of 18, he married Anne Hathaway, with whom he had three children: Susanna, and twins Hamnet and Judith. Between 1585 and 1592, Shakespeare began a successful career in London as an actor, writer, and part-owner of a playing company called the Lord Chamberlain’s Men, later known as the King’s Men. He appears to have retired to Stratford around 1613 at age 49, where he died three years later on 23 April 1616. Few records of Shakespeare’s private life survive, and there has been considerable speculation about such matters as his physical appearance, sexuality, religious beliefs, and whether the works attributed to him were written by others. Shakespeare produced most of his known work between 1589 and 1613. His early plays were mainly comedies and histories and these works remain regarded as some of the best work produced in these genres. He then wrote mainly tragedies until about 1608, including Hamlet, Othello, King Lear, and Macbeth, considered some of the finest works in the English language. In his last phase, he wrote tragicomedies, also known as romances, and collaborated with other playwrights.

Many of his plays were published in editions of varying quality and accuracy during his lifetime. In 1623, John Heminges and Henry Condell, two friends and fellow actors of Shakespeare, published the First Folio, a collected edition of his dramatic works that included all but two of the plays now recognized as Shakespeare’s. It was prefaced with a poem by Ben Jonson, in which Shakespeare is hailed, presciently, as not of an age, but for all time. In the 20th and 21st century, his work has been repeatedly adopted and rediscovered by new movements in scholarship and performance. His plays remain highly popular today and are constantly studied, performed, and reinterpreted in diverse cultural and political contexts throughout the world. The Shakespeare authorship question is the argument that someone other than William Shakespeare of Stratford-upon-Avon wrote the works attributed to him. Anti-Stratfordians – a collective term for adherents of the various alternative-authorship theories – say that Shakespeare of Stratford was a front to shield the identity of the real author or authors, who for some reason did not want or could not accept public credit. Although the idea has attracted much public interest, all but a few Shakespeare scholars and literary historians consider it a fringe belief and for the most part acknowledge it only to rebut or disparage the claims. Shakespeare’s authorship was first questioned in the middle of the 19th century, when adulation of Shakespeare as the greatest writer of all time had become widespread. Shakespeare’s biography, particularly his humble origins and obscure life, seemed incompatible with his poetic eminence and his reputation for genius, arousing suspicion that Shakespeare might not have written the works attributed to him. The controversy has since spawned a vast body of literature, and more than 80 authorship candidates have been proposed, the most popular being Sir Francis Bacon; Edward de Vere, 17th Earl of Oxford; Christopher Marlowe, William Stanley, 6th Earl of Derby and Lewis Theobald. Supporters of alternative candidates argue William Shakespeare lacked the education, aristocratic sensibility, or familiarity with the royal court that they say is apparent in the works. Those Shakespeare scholars who have responded to such claims hold that biographical interpretations of literature are unreliable in attributing authorship, and that the convergence of documentary evidence used to support Shakespeare’s authorship – title pages, testimony by other contemporary poets and historians, and official records – is the same used for all other authorial attributions of his era. Keep in mind, that no such direct evidence exists for any other candidate, and Shakespeare’s authorship was not questioned during his lifetime or for centuries after his death. Finally, 21st Century technology appears to have found a methodology for confirming the great bard’s accomplishments of creative genius.

Shakespeare is such a towering literary figure that any new insight into the man, or his work, tends to generate a jolt of excitement in academic and non-academic communities of Shakespeare aficionados. Applying psychological theory and text-analyzing software, researchers at the University of Texas at Austin have discovered a unique psychological profile that characterizes Shakespeare’s established works, and this profile strongly identifies Shakespeare as an author of the long-contested play Double Falsehood. The findings are published in Psychological Science, a journal of the Association for Psychological Science. Research in psychology has shown that some of the core features of who a person is at their deepest level can be revealed based on how they use language. With our new study, we show that you can actually take a lot of this information and put it all together at once to understand an author like Shakespeare rather deeply, says researcher Ryan Boyd of the University of Texas at Austin. The study, conducted in collaboration with James Pennebaker, also at UT-Austin, goes beyond examining authorship from the standpoint of word counts and linguistic regularities, providing a deeper exploration of an author’s psychological profile. This research shows that it is indeed possible to start modeling peoples’ mental worlds in much more complete ways. We don’t need a time machine and a survey form to figure out what type of person Shakespeare was — we can determine that very accurately just based on how he wrote using methods that are objective and easy to do, Boyd explains.

Double Falsehood was published in 1728 by Lewis Theobald, who claimed to have based the play on three original Shakespeare manuscripts. The manuscripts have since been lost, presumably destroyed by a library fire, and authorship of the play has been hotly contested ever since. Some scholars believe that Shakespeare was the true author of Double Falsehood, while others believe that the play was actually an original work by Theobald himself that he tried to pass off as an adaptation. Boyd and Pennebaker realized that using psychological theory to inform analysis of the playwrights’ respective works may shed light on the authorship question. They examined 33 plays by Shakespeare, 12 by Theobald, and 9 by John Fletcher, a colleague (and sometime collaborator) of Shakespeare. The texts were stripped of extraneous information (such as publication information) and were processed using software that evaluated the works for specific features determined prospectively by the researchers. For example, the researchers’ software examined the playwrights’ use of function words (e.g., pronouns, articles, prepositions) and words belonging to various content categories (e.g., emotions, family, sensory perception, religion). They had the software identify themes present in each of the works to generate an overarching thematic signature for each author. They also examined the works to determine how categorical the writing was. Categorical writing tends to be heavy on nouns, articles, and prepositions, and it indicates an analytic or formal way of thinking. Research has shown that people who rate high on categorical thinking tend to be emotionally distant, applying problem-solving approaches to everyday situations. People who rate low on categorical thinking, on the other hand, tend to live in the moment and are more focused on social matters.

By aggregating dozens of psychological features of each playwright, Boyd and Pennebaker were able to create a psychological signature for each individual. They were then able to look at the psychological signature of Double Falsehood to determine who the author was most likely to be. Looking at the plays as whole units, the results were clear: Every measure but one identified Shakespeare as the likely author of Double Falsehood. Theobald was identified as the best match only when it came to his use of content words, and even then only by one of the three statistical approaches the researchers used. When Boyd and Pennebaker broke the play down into acts and analyzed the texts across acts, they found a more nuanced picture. For the first three acts, the analyses continued to identify Shakespeare as the likely author; for the fourth and fifth acts, the measures varied between Shakespeare and Fletcher. Again, Theobald’s influence on the text appeared to be very minor. Honestly, I was surprised to see such a strong signal for Shakespeare showing through in the results, says Boyd. Going into the research without any real background knowledge, I had just kind of assumed that it was going to be a pretty cut and dry case of a fake Shakespeare play, which would have been really interesting in and of itself. By using measures that tapped into the author’s psychological profile, Boyd and Pennebaker were able to see that the author of Double Falsehood was likely sociable and fairly well educated — findings that don’t jibe with accounts of Theobald as well educated but also rigid and abrasive. Together, these findings clearly show that exploring the psychological dimensions of a literary work can offer even deeper insight in the process of textual analysis.

I’ve always held huge admiration for scholars who grapple with literature — there is a great deal of detective work that goes into figuring out who the authors really are ?deep down,’ their motivations, their lives, and how these factors are embedded within their work, says Boyd. We demonstrate with our current work that an incredible amount of this information can be extracted automatically from language.

Apr

20

About 30,000 Americans have small intestinal carcinoid tumors. Like most cancers, early treatment greatly increases survival rates and quality of life. Small intestinal carcinoid tumors are rare and most grow very slowly. Most of them occur in the small intestine, rectum, and appendix. Sometimes more than one tumor will form. Small intestinal carcinoid tumors form from a certain type of neuroendocrine cell (a type of cell that is like a nerve cell and a hormone -making cell). These cells are scattered throughout the chest and abdomen but most are found in the GI tract. Neuroendocrine cells make hormones that help control digestive juices and the muscles used in moving food through the stomach and intestines. A small intestinal carcinoid tumor may also make hormones and release them into the body.

According to an article published online in Gastroenterology (9 April 2015), heredity accounts for up to 35% of small intestinal carcinoid tumors. Because the disease has long been considered randomly occurring rather than inherited, people with a family history were not typically screened. To answer the question, the study examined families with a history of the disease. The study, conducted at the NIH Clinical Center, the study screened 181 people from 33 families, each with at least two cases of small intestinal carcinoid. Genetic linkage analysis revealed a target DNA region shared by all affected members of a particularly large family. Genome sequencing narrowed that finding to a gene defect passed from one generation to the next, suggesting that the gene is an inherited risk factor for the disease. Disease was also discovered in 23 people who had not yet developed symptoms, and tumors were successfully removed in 21 of those people.

Apr

20

After alcohol is consumed, it is first metabolized into acetaldehyde, a toxic chemical that can cause DNA damage and cancer. In the liver, aldehyde dehydrogenase 2 (ALDH2) is the main enzyme responsible for breaking down acetaldehyde into acetate, a nontoxic metabolite. It also removes other toxic aldehydes that can accumulate in the body. An estimated 560 million people in East Asia, and many people of East Asian descent, carry a genetic mutation that produces an inactive form of ALDH2. When individuals with the ALDH2 mutation drink alcohol, acetaldehyde accumulates in the body, resulting in facial flushing, nausea, and rapid heartbeat. People with the ALDH2 mutation are also at increased risk for cancers of the mouth, esophagus, and other areas of the upper aerodigestive tract.

According to an article published online in the Proceedings of the National Academy of Sciences (10 March 2015), an experimental compound empowers an enzyme to help process acetaldehyde, and this finding may lead to new treatments to help people with impaired ability to metabolize acetaldehyde and other toxic substances. These small molecules called aldehyde dehydrogenase activators, or Aldas, have been found to increase the activity of the ALDH2 enzyme in previous studies.

In the current study, the authors tested a new compound, Alda-89, which they found could provide another aldehyde dehydrogenase enzyme – ALDH3A1 — with accelerated acetaldehyde-metabolizing powers that it ordinarily does not possess. The authors targeted the ALDH3A1 enzyme because it metabolizes acetaldehyde poorly and is highly expressed in the upper airway, stomach and gut, all tissues that are prone to cancer development in people who drink alcohol in excess. According to the authors, by recruiting ALDH3A1 to metabolize acetaldehyde, it may be possible to accelerate the elimination of acetaldehyde from tissues that are more vulnerable to its carcinogenic effects. Results from the study showed that Alda-89 increased acetaldehyde metabolism both in normal mice and in mice carrying the ALDH2 mutation found in the East Asian population. The authors also showed that, in test tube analyses, acetaldehyde removal was faster when they combined Alda-89 with Alda-1, a compound previously shown to activate ALDH2, compared with activating each ALDH alone. Studies also showed that mice treated with the combination of Alda-89 and Alda-1 exhibit accelerated recovery from alcohol intoxication.

Apr

20

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions). Over time, recovery periods may be incomplete, leading to progressive decline in function and increased disability. MS patients often experience muscle weakness and difficulty with coordination and balance. Most people experience their first symptoms of MS between the ages of 20 and 40.

The FDA has approved the first generic version of Copaxone (glatiramer acetate injection), used to treat patients with relapsing forms of multiple sclerosis (MS). For the approval, FDA scientists established a thorough scientific approach for demonstrating active ingredient sameness that takes into consideration the complexity of glatiramer acetate. This approach was documented in the 43 page Citizen Petition Denial Letter From CDER to Teva Pharmaceuticals which is worthwhile reading.

In the clinical trials for Copaxone, the most common adverse reactions reported by those taking Copaxone were skin problems at the injection site (redness, pain, swelling and itching), flushing (vasodilation), rash, shortness of breath and chest pain.

On your already oiled baking sheet, place each zucchini circle in a row of separate circles. Don’t overlap any of the circles; keep them in a single layer. If you run out of space, use another oiled baking sheet.

Bake the zucchini circles until they’re golden brown with crispy edges. This should take about 10 to 15 minutes, on each side, depending on your oven. Flip them over after they start to turn golden and bake the other side.

When done, remove from the baking sheet to a pre-warmed serving plate or platter and serve immediately. With these zucchini circles, serve some warm marinara sauce and extra, freshly grated parmesan. Or plain is equally good. Some people like a little fresh lemon juice squeezed over the circles.

We started our Friday with icy Fume Blanc and the zucchini circles, big plate between us, we speared the zucchini with little forks. Yum! Next our favorite Ugli Salad with tiny green olives, fresh lemon juice and good olive oil. Next came one of Jules’ favorites, tuna casserole and kale patties. Dessert was a new experiment, individual ramekins with a tiny rum cake and cool whip on top. The beginning of a lovely weekend.

Flowers are out, in front of our building. I especially look forward to the Southern Magnolia tree. We have a resident extended family of sparrows living in a nearby thick vine climbing up one wall and I love to hear them chirping all day. The white blossoming pear trees are nearly in full bloom up and down the full length of Park Avenue. Soon the flowering crab trees will open up next to them, and together they create a pink and white cloud of beauty so ephemeral, easily missed. We drove past all this, on our way to the theater, to see, Nathan Lane in, It’s Only A Play by Terrance McNally. Although, the play itself is hollow and tepid, the cast was so good, I found myself laughing out loud several times. When Nathan Lane is good, he is really, really good and I have always loved Stockard Channing. A British actor played the part of a play director and I found his wildly energetic performance wonderfully ridiculous. I even liked him better than Nathan Lane. The constant name dropping of mostly theatrical celebrities got to be a little much, but in a tacky sort of way, it fit this play. One memorable line was: Ifyou took theater out of New York, you’d have Newark. We had a good time!

We had dinner at Sardi’s which is one of the few NY restaurants, recommended for tourists, where regular New Yorkers like us still like to go, and where actors still go after their evening show. Excellent service, good food, always fun here!